Agents potentially affecting cell surface structures are designed, synthesized, and examined for anti-cancer activity in mouse tumor model systems including L1210 leukemia, Friend erythroleukemia, and Ehrlich carcinoma in vivo and in vitro. Active agents are subjected to detailed biochemical and immunological studies to ascertain mechanisms by which anti-cancer effects are obtained. Active agents at this point include esters of 1-chloro- and 1-bromo-3-hydroxyacetone (benzoate, p-nitrobenzoate, and 3,5-dinitro-benzoate), and N-halo-acetyl-galactosamine) as the lipophilic tetra-O-acetates. These agents cure Ehrlich carcinoma in vivo by single injection if host animals are immune-competent. Such animals exhibit strong resistance to rechallenge. Friend erythroleukemia cells treated in culture with 1-chloro-3-hydroxyacetone benzoate (C1HAB) and implanted into syngeneic host mice, confer protective immunity to rechallenge with Friend leukemia cells. Under similar conditions of chemical treatment in vitro followed by reimplantation, L1210 leukemia cells enhance tumor growth upon rechallenge in semisyngeneic BDF1(db) (DBAx C51B1/6) hosts. This enhancement extends also to mice injected with X-irradiated L1210 cells. The detailed definition of this enhancement phenomenon is under investigation. The effect is produced by as few as 100 L1210 cells, it appears as early as 24 hours after exposure, lasts at least 10 weeks, does not appear in syngeneic DBA hosts nor in DBAxBalb/C (dd) hybrid hosts, does not affect P815 growth in BDF1 hosts, but strongly enhances growth of Ehrlich carcinoma in BDF1 mice. We postulate that the chemotherapeutically active halohydroxyacetone esters exert their effects as lipophilic alkylating agents reactive initially with cell surface thiol groups, but possibly also by acting as bifunctional reagents. Analogs testing with importance of both hydrophobicity and difunctionality are being synthesized.